Help us: Donate
Follow us on:
Γ—

Menu

Back

Gene Therapy Ameliorates Sarcopenia in Old Mice

Many of the benefits were sex-specific.

Treadmill mouseTreadmill mouse

A paper published in Aging has detailed how gene therapy has been used to treat sarcopenia in wild-type mice, and the results are positive.

A lack of effective treatments

As expected with papers of this kind, the researchers begin by discussing frailty and sarcopenia, the age-related loss of muscle tissue that is associated with decreased mobility and an increased risk of falls. The researchers note that there are not yet any real medical treatments for sarcopenia and that current attempts to intervene only involve exercise and nutrition, which are moderately effective in slowing this disease but cannot stop its basic causal factors.

We have previously written about the development of gene therapy for sarcopenia focusing on the enzyme PCYT2. These researchers use a similar approach, but they focus on a different target: neurotrophin-3 (NT-3), which has been previously shown to improve muscle fiber thickness and many other parameters in mouse models [1, 2]. That previous work, however, used mouse models of a genetic disease. This experiment used naturally aged wild-type mice.

Straight to the muscles

The researchers selected a skeletal muscle-specific promoter to make sure that this gene therapy affects only the right kind of tissue. The treatment was injected directly into the gastrocnemius, a calf muscle that is a major part of locomotion. The mice used in this experiment were 18 months old when it began and were tested two, four, and six months after injection.

These mice were put on a treadmill and run to exhaustion. As expected, the treated mice lasted significantly longer than the untreated mice at all three tested time periods, with the strongest results being four months after injection: the treated mice ran roughly twice as far. In a rotarod experiment, which is used to evaluate motor control, treated mice performed better, and their twitch strength was also found to be higher. The mice’s total weight was almost entirely unaffected.

Interestingly, although male mice still received a substantial benefit, female mice seemed to respond much better than males at four months in the treadmill experiment. This was accompanied by sex-specific fiber changes in different muscle groups. Some muscle groups in females were found to change in their proportions of fast-twitch and slow-twitch fibers, while the same groups in their male counterparts changed in an opposite way or did not change at all.

Nerves and mitochondria more like those of young mice

However, despite the muscle-specific nature of the treatment, the nerves of the treated mice were found to be substantially more youthful in at least one key respect. Myelin, the protective and functional coating of nerves, decreases with age. In the distal tibial nerve, which is connected to the muscle tissue that is the focus of this study, two-year-old untreated mice had substantially thinner myelin than their one-year-old counterparts.

This age-related problem was almost completely reversed in the treated group. In this specific nerve, two-year-old treated mice had myelin thickness that was very close to one-year-old untreated mice. Neuromuscular junctions in the area were also found to be improved.

The mitochondria of the treated group were also found to be more youthful in their overall prevalence, although carbohydrate use was found to be sex-specific in a way that matched the changes in fiber type. This was connected to the aging-related factor mTORC1, which was affected substantially more in females than males.

Conclusion

Some of this study’s findings are puzzling and poorly explained, some aspects of the basic biology are not fully eludicated, and it is not known why this approach is so much more effective in female mice than male ones. However, the results of this study were still significantly positive. Combining this target with other genes that affect aging, developing a gene therapy combination, may be the right path for effectively treating sarcopenia in human beings.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

Vitalik Buterin Exclusive Interview: Longevity, AI and More

Vitalik Buterin holding Zuzu, the puppy rescued by people of Zuzalu. Photo: Michelle Iai Don’t try finding Zuzalu on a...

Centenarians Have Slightly Different Gut Ecologies

Researchers publishing in Nature Microbiology have determined that the viruses populating the intestines of centenarians are slightly different from those...

Hypoxia Extends Median Lifespan in Fast-Aging Mice by 50%

Scientists have found that continuous oxygen restriction drastically extends the lifespan of progeroid mice, but the effect's mechanism remains a...

Discovering Why Adrenal Cancer Is More Dangerous for Women

A paper published today in Nature Aging has explained a relationship between cellular senescence, cancer of the adrenal glands, and...

Literature

[1] Yalvac, M. E., Amornvit, J., Chen, L., Shontz, K. M., Lewis, S., & Sahenk, Z. (2018). AAV1. NT-3 gene therapy increases muscle fiber diameter through activation of mTOR pathway and metabolic remodeling in a CMT mouse model. Gene therapy, 25(2), 129-138.

[2] Ozes, B., Moss, K., Myers, M., Ridgley, A., Chen, L., Murrey, D., & Sahenk, Z. (2021). AAV1. NT-3 gene therapy in a CMT2D model: phenotypic improvements in GarsP278KY/+ mice. Brain Communications, 3(4), fcab252.

CategoryNews
About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called β€œreal life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
No Comments
Write a comment:

*

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.